Breast cancer is the most prevalent non-skin cancer in women in the US. To increase the early detection of breast cancer, annual screening mammography has been recommended for asymptomatic patients. However, mammography is not without limitations. The superposition of glandular tissue is an inherent consequence of the two dimensional nature of mammography, and may result in the masking of lesions of interest (reducing sensitivity) or the false appearance of overlapping normal tissues as lesions (reducing specificity). Digital tomosynthesis of the breast is a novel x-ray based imaging technique being investigated to replace mammography for the early detection and diagnosis of breast cancer. Tomosynthesis is based on the concept of limited angle computed tomography, in which projections of the imaged object acquired from a limited angular range give enough information to partially reconstruct that object in three dimensions. Reports indicate that tomosynthesis reduces callback rate (increasing specificity) and increases detection rate (increasing sensitivity) compared to mammography. However, in current implementations of breast tomosynthesis, the breast undergoes the same vigorous compression as that used in mammography. It has been shown that the pain resulting from this vigorous breast compression during mammography is an important factor in women not undergoing the recommended annual screening mammography. This reduction in screening adherence results in an increase in breast cancer mortality and in a reduction in treatment options, yielding a higher number of mastectomies as opposed to breast conserving surgeries. The objective of this research project is to develop and test new image acquisition and processing techniques that will allow for the acquisition of breast tomosynthesis images with a substantial reduction in the amount of breast compression used with no loss in image quality or increase in radiation dose. For this, we will (1) develop a method to reduce the impact of x-ray scatter on image quality; (2) develop new image acquisition techniques for reduced compression tomosynthesis that result in the same radiation dose and image noise levels as standard tomosynthesis; (3) compare the image quality between standard tomosynthesis and reduced compression tomosynthesis performed with the techniques developed in this project. Successful completion of this project will result in the ability to perform breast tomosynthesis imaging with substantially reduced breast compression levels, with no increase in radiation dose, and no loss in image quality and tissue coverage. This will result in a reduction in the pain associated with breast cancer screening, resulting in an increase in screening adherence by women, which will decrease breast cancer mortality and increase the number of cases in which breast conserving surgery can be performed.